A study finds the first genetic links that predict timing of menopause.

Researchers from the University of California, San Francisco (UCSF) found that women with mutations in the BRCA1 or BRCA 2 genes, which are associated with an up to five times higher risk of developing breast and ovarian cancers, were more likely to enter menopause early compared to women without the gene. The finding, reported in the journal Cancer, has important implications for women trying to get pregnant, since those with the genetic mutations may be more vulnerable to infertility.

The study included 400 female BRCA gene carriers in northern California and compared the timing of their menopause onset to 765 women without the gene mutation from the same region. They found that the BRCA carriers were likely to enter menopause on average at age 50, compared to age 53 for the other women.

“What is really complicated about these patients is that because they have a higher risk of breast and ovarian cancer, they’re under a lot of surveillance and a lot of pressure to remove breast tissue and ovaries to reduce cancer risk,” says senior study author Dr. Mitchell Rosen, director of the UCSF Fertility Preservation Center and associate professor in the UCSF Department of Obstetrics, Gynecology and Reproductive Sciences. Still, Rosen and his team found early menopause among women with the BRCA mutations who had not undergone surgery to remove their ovaries, and other studies have shown that these women may be prone to ovarian failure, possibly related to the effects of their genetic changes.

For smokers, the findings are even more somber. Smoking has been known to alter estrogen levels and menstrual cycles, and the researchers found that women who were considered heavy smokers—smoking over 20 cigarettes a day—tended to experience menopause even earlier, at around age 46.

The research adds an additional dilemma for women carrying the gene who still want a family, and may even help to identify new genetic factors underlying infertility. “This means there may be other similar genes that need further investigation to determine whether [carriers] are more likely to experience infertility as they get older.”

Additional studies are needed to confirm and build upon on these findings. Even in the current study, only 166 women with BRCA mutations who did not have a hysterectomy and thus experienced natural menopause were included; finding larger numbers of women who chose not to have surgery is challenging, so the data on age of natural menopause for BRCA carriers is limited.

Based on their findings, however, the researchers believe that women who carry either BRCA 1 or BRCA 2 should be aware that they may be at higher risk of infertility and early menopause, and consider having children sooner. While sobering, the information could help more women to have families when they can, before they start to experience problems with infertility.